Menopause is the transitional phase in a woman's life when menstrual function ceases and can result from natural or induced changes in the body. Natural menopause results from declining ovarian function due to aging of the ovaries which become atrophic and usually occurs between ages 40 and 50. Occasionally ovarian function ceases prior to age forty resulting in premature menopause.
It is believed that the symptoms of menopause are due primarily to estrogen deficiency since when menopause occurs there is a marked decrease in ovarian estrogen production and since the administration of estrogens, for example, diethylstibestrol, conjugated estrogens or estradiol provide a specific and effective manner of treatment. However, it is becoming increasingly apparent that estrogenic products currently in use possess certain undesirable side effects which must be set against the undoubted benefits resulting from their use. For example, diethystilbestrol, a once widely used and well established estrogen, has been implicated as possibly being responsible for vaginal cancer and adenosis of the female offspring of pregnant women treated with the compound (Lancet 1975, 1960). Also, ethinyl estradiol and mestranol, which represent estrogenic components in current oral contraceptives are now known to be involved in certain serious side effects associated with oral contraceptives including depression, (Nature 243, 58 (1973)), hypertension (Am. J. Obstet. Gynecol. 112, 912 (1972)), carbohydrate and lipid abnormalities (Lancet 1969, Oct. 11, 783), interference with blood clotting mechanism resulting in thrombosis and stroke (Ann. Intern Med. 72, 111 (1970)), and jaundice (Am. J. Obstet. Gynecol. 119, 165 (1974)). Also, the administration of estrogens to post-menopausal women has been implicated as a cause of endometrial cancer (Science 191, 838 (1976)). Consequently, there is a need for an improved method of treating menopause.
The present invention provides a novel and improved method of treating the symptoms of menopause and osteoporosis which comprises administering androstene compounds described more fully hereinbelow. Some of the compounds employed in the present invention, for example, 19-hydroxyandrost-4-ene-3,17-dione and the 19-oxo derivative thereof have been involved in numerous in vitro studies wherein their role in the metabolism of androgens has been investigated. Additionally, 19-hydroxyandrost-4-ene-3,17-dione is reported to have been administered to two healthy male subjects each 21 years of age (J. Clin. Endocrinol. Metab. 28, 1401 (1968)). Also, 3-oxo-17.beta.-hydroxyandrost-4-en-19-al has been reported in U.S. Pat. No. 3,235,573 issued Feb. 15, 1966 and U.S. Pat. No. 3,449,381 issued June 10, 1969 wherein the utilities disclosed are anabolic-androgenic activity, inhibition of pituitary gonadotrophins and adrenocorticotrophin, antiestrogenic, blood, liver and adrenal cholesterol lowering properties, control of fertility and psychotic changes, and appetite stimulants. To applicant's knowledge, the use of the compounds employed in the present invention in the treatment of the symptoms of menopause or osteoporosis has not been taught or suggested heretofore.